Migraine headache is a primary disorder unrelated to another condition such as an injury or malignancy. Sufferers usually can't participate in normal activities during an attack because of the intensity of the pain. It is estimated that more than 100 million work days and $13 billion are lost annually, in the U.S. alone, due to migraine-induced disability. The duration of attacks lasts for hours to days and with about 14 million sufferers or “chronic migraineurs” being affected for a minimum of 15 days per month. Because migraine has such a long and pandemic global history of documented occurrence, a vast array of remedies preceded the development of modern pharmaceutical interventions. These included nutritional, herbal and plant-based ingredients, some of which provided documented beneficial effects.
Common dietary food items were often employed. For example, salmon, (balanced omega 3-6-9 fatty acid profile to combat inflammation), figs (high in potassium combined with other electrolytes), shrimp (astaxanthin-antioxidant and anti-inflammatory), as well as carrots, sweet potato, kale and collard greens (high carotenoid and phytochemical content) have been consumed in hopes of mitigating migraine headache. While not a formal part of the current invention, these foods are recommended as adjunctive measures for migraineurs to utilize. In this invention, certain herbals and other nutrients are included because they are highly effective, although their mechanisms of action may not yet be fully elucidated. Many of these plant-based therapies have proven to be efficacious both in validated clinical experience as well as in some peer-reviewed human trials. Those with the most durable benefits have been incorporated and include basil, butterbur, ginger, feverfew, mints (mentha spp.) and valerian.
In selecting herbals and phytonutrients, the inventors considered documented experiential evidence relative to migraine headache. The following nutrients were examined but specifically excluded because they ultimately had less scientific support and justification for their efficacy or may have represented particular safety concerns: coriander seed (Coriandrum sativum), with anti-inflammatory potential, lavender oil (Lavandula angustifolia) inhalation thought to promptly relieve symptoms, rosemary (Rosmarinus officinalis), linden, lime tree (Tilia spp.), horseradish (Armoracia rusticana) with vascular narrowing properties, honeysuckle (Lonicera japonica) with anti-inflammatory pain relief, yarrow (Achillea millefolium), teaberry (Gaultheria procumbens, “wintergreen”) with potential to treat neuralgias, hops (Humulus lupulus), with sedative effects, betony (Stachys officinalis), to relieve facial swelling and pain, boswellia (Indian frankincense) with AKBA, turmeric, with anti-inflammatory curcuminoids, and willow (Salix spp.), with anti-inflammatory salicin.
To construct the most appropriate formulation to impact migraine headache, the dominant mechanisms of action had to be addressed. Neurogenic inflammation, vascular dilation and cytokine release are among those that impact migraine pathophysiology and pharmacology and represent potential therapeutic targets. Relative to the current invention, the ketone body, 3-hydroxybutyrate has shown beneficial effects by reducing inflammation. This is important because most treatments lose efficacy with increased use over time while often causing adverse side effects. These therapies and their problematic accompanying effects are well described in the related “parent” patent to this “continuation-in-part” application. The rather extensive list includes non-steroidal anti-inflammatory drugs, narcotic analgesics, steroids, beta blockers, triptans, serotonergic agents, calcium channel blockers, ergotamines, tricyclic antidepressants, anticonvulsants, and occasionally in desperation, botulinum toxin. These compounds have also been excluded from this invention. Most recently, three pharmaceutical classes have been in development for migraine including calcitonin gene-related peptide (CGRP) inhibitors, gepants (oral CGRP receptor antagonists) and ditans (serotonin 5-HT receptor agonists). These new drugs are very expensive and current trials have shown at best only modest effect while the long-term safety profiles have in no manner been ascertained.
These realities added to the daunting spectrum of severe side effects from current treatment approaches clearly demonstrate the need for safer therapies to prevent or reduce frequency of migraine onset and minimize symptoms. Ketogenesis has been proposed as a beneficial strategy for migraineurs but adherence to a true ketogenic diet can be challenging. Another path is possible since providing KMCT to sufferers can reduce frequency of migraine onset and symptoms. The KMCT may comprise a mixture of capric and caprylic triglycerides and/or are enriched or purified from coconut oil as a parent source. KMCT are metabolized in the liver to provide a rich supply of ketone bodies, which can be metabolized as a carbon and energy source for the body, especially the brain. Providing exogenous KMCT does not result in adverse physiological effects or compliance issues associated with ketogenic dieting. Ingestion of KMCT has no reported serious side effects and only transitory gastro-intestinal distress or sensitivity in some users is noted. Thus, this approach can prevent or reduce the frequency of migraine headache onset, reduce symptom severity and augment benefits from other pharmaceutical (e.g. as listed previously in this section) or non-pharmaceutical interventions (e.g. such as some agents included in this formulation listed in a subsequent section). In addition, dietary ketones can be provided by ketone esters, ketone salts and/or combinations thereof and raise plasma ketone body levels to clinically effective ranges.
Two factors further contributing to the severity of the migraine headache issue are oxidative stress and inflammation. Oxidative damage from excess free radicals is generated by normal metabolism including neuro-physiological and hormonal stress, as well as a diverse number of external factors affecting human health including air pollution, occupational exposures, physical activity, radiation and smoking. This oxidative stress may injure cells, tissues, organs and body proteins, lipids and DNA. If they damage non-dividing cells such as neurons, it may result in neurological conditions possibly including the migraine headache complex. While antioxidants and antioxidant enzymes may be protective, there is also potential for hormones and natural substances to be beneficial and these therapeutic categories may be effectively combined to achieve the best outcomes. In addition to excess free radicals, acute and chronic inflammatory reactions also contribute to the spectrum of injury. Therefore, while many sources may cause injury, only a few common mechanisms are involved. This provides the current invention an opportunity to eliminate or reduce the impact of migraine headache by employing the benefits of antioxidants, hormones, phytochemicals and additional nutrients.
While a standard “Western” diet can promote normal growth and development, foods may also contain naturally occurring toxic as well as protective substances, and the relative levels of these competing elements may be critical. Mutagens and carcinogens are formed during digestion and studies suggest that vitamin C and E consumption reduces the formation of mutagens in the small intestine during this process with the combination of the two being more effective than each antioxidant individually. These antioxidant vitamins are included in the present formulation.
With this background, it is the intent of the current invention to expand the previous application relative to ketogenic sources and the beneficial impact they have on the migraine headache spectrum. These complex formulations aim to maximize the potential health effects beyond ketogenesis alone by combining a broader platform of micronutrients from multiple sources including phytochemicals from plant herbals and their derivatives, vitamins, antioxidants, minerals and other nutrients. It was developed for wide human use from age twelve years and older. The formulation is intended to reduce portions of the initiating and sustaining causes of migraine headache including oxidative damage and inflammation while potentially enhancing neuroprotection.